Journal of Interferon and Cytokine Research最新文献

{"title":"Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.","authors":"Martti Vanker, Karita Särekannu, Arnaud Fekkar, Sofie Eg Jørgensen, Liis Haljasmägi, Anne Kallaste, Kalle Kisand, Margus Lember, Pärt Peterson, Madhvi Menon, Tracy Hussell, Sean Knight, James Moore-Stanley, Paul Bastard, Shen-Ying Zhang, Trine H Mogensen, Quentin Philippot, Qian Zhang, Anne Puel, Jean-Laurent Casanova, Kai Kisand","doi":"10.1089/jir.2023.0003","DOIUrl":"10.1089/jir.2023.0003","url":null,"abstract":"<p><p>Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; <i>P</i> < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"379-393"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>IFNL4</i> Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.","authors":"Francine S Baker, Jeanny Wang, Oscar Florez-Vargas, Nathan R Brand, Martin D Ogwang, Patrick Kerchan, Steven J Reynolds, Constance N Tenge, Pamela A Were, Robert T Kuremu, Walter N Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Ismail D Legason, Hadijah Nabalende, George Chagaluka, Nora Mutalima, Eric Borgstein, George N Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M Molyneux, Robert Newton, Ludmila Prokunina-Olsson, Sam M Mbulaiteye","doi":"10.1089/jir.2023.0014","DOIUrl":"10.1089/jir.2023.0014","url":null,"abstract":"<p><p>Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the <i>IFNL4</i> gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (<i>IFNL4</i>-dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of <i>IFNL4</i>-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between <i>IFNL4</i> genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, <i>P. falciparum</i> infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within <i>IFNL4</i> (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of <i>IFNL4</i>-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"394-402"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Monoclonal Antibodies to Measure Cell Surface Protein Levels of Human Interferon-Lambda Receptor 1.","authors":"Nicole A de Weerd,&nbsp;Olamide Ogungbola,&nbsp;Xinyun Liu,&nbsp;Antony Y Matthews,&nbsp;Amina Ismail,&nbsp;Julian P Vivian,&nbsp;San S Lim,&nbsp;D Lorne Tyrrell,&nbsp;Niru Putcha,&nbsp;Mike Skawinski,&nbsp;Harold Dickensheets,&nbsp;Thomas B Lavoie,&nbsp;Raymond P Donnelly,&nbsp;Paul J Hertzog,&nbsp;Deanna M Santer","doi":"10.1089/jir.2023.0040","DOIUrl":"10.1089/jir.2023.0040","url":null,"abstract":"<p><p>Type III interferons (IFN-lambdas, IFN-λs) are important antiviral cytokines that can also modulate immune responses by acting through a heterodimeric receptor composed of the specific and limited expressed IFN-λR1 chain and the ubiquitous IL-10R2 chain, which is shared with IL-10 family cytokines. Conflicting data have been reported regarding which cells express the IFN-λR1 subunit and directly respond to IFN-λs. This is, in part, owing to transcript levels of the IFN-λR1 gene, <i>IFNLR1</i>, not always correlating with cell surface protein levels. In this study, we tested a panel of novel monoclonal antibodies (mAbs) that specifically recognize human IFN-λR1. Initially, antigen specificity was confirmed by enzyme-linked immunosorbent assay (ELISA), from which a subset of antibodies was selected for additional flow cytometry and neutralization assays. We further characterized two antibodies based on their strong ELISA binding activity (HLR1 and HLR14) and found only HLR14 could reliably detect cell surface IFN-λR1 protein on a variety of cell lines by flow cytometry. HLR14 could also detect IFN-λR1 protein on certain primary human blood cells, including plasmacytoid dendritic cells and B cells from peripheral blood. Availability of the HLR14 mAb will enable the quantification of IFN-λR1 protein levels on cells and better characterization of the cell specificity of the IFN-λ response.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"403-413"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles and Effects of Interferon Lambda Signaling in the Context of Bacterial Infections.","authors":"Da'Kuawn Johnson, Nicholas Carbonetti","doi":"10.1089/jir.2023.0037","DOIUrl":"10.1089/jir.2023.0037","url":null,"abstract":"<p><p>Type III interferon, or interferon lambda (IFNλ), was discovered 20 years ago and has been studied primarily for its role in combatting viral infections. However, it is also induced in response to certain bacterial infections but its roles and effects in this context are relatively poorly understood. In this mini review, we discuss the roles of IFNλ signaling in bacterial infections, highlighting its deleterious or protective effects for different infections. We also discuss a couple of recent studies showing that some bacteria possess defense mechanisms against the effects of IFNλ. We hope that this review will spur further investigation into the roles of IFNλ in the context of bacterial infections and will promote considerations of its therapeutic potential for these infections.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"363-369"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation.","authors":"Emily V Mesev, Emma G Guare, Alexander Ploss, Jared E Toettcher","doi":"10.1089/jir.2023.0039","DOIUrl":"10.1089/jir.2023.0039","url":null,"abstract":"<p><p>Type III interferons (IFN-λ) are central to host defense against viral infection of epithelial barrier surfaces. IFN-λ binding to its receptor induces a JAK-STAT cascade through kinases Janus-associated kinase 1 (JAK1) and tyrosine kinase 2 (TYK2), which are associated on either subunit of the heterodimeric type III IFN receptor. Recent studies have shown that TYK2 is not necessary for IFN-λ to signal, in contrast to IFN-α, which uses the same JAK-STAT pathway activated by the type I IFN receptor. The mechanism for this differential TYK2 requirement is unknown. Our study uses synthetic IFN receptors in TYK2-deficient U2OS epithelial cells to define the processes in type I and III IFN signaling that require TYK2. We find that TYK2 deficiency reduces signaling equally from heterodimers of either type I or III IFN receptor intracellular domains. In contrast, JAK1-associated homodimers of IFNAR2 or IFNLR1 are both fully signaling competent even in the absence of TYK2. These results suggest that heterodimerization of the type III IFN receptor is insufficient to confer TYK2-independent signaling. Thus, we propose that noncanonical receptor complexes may participate in endogenous type III IFN signaling to confer TYK2-independent signaling downstream of IFN-λ stimulation.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"414-426"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interferon-Lambda Family Celebrates 20 Years of Scientific Discovery.","authors":"Raymond P Donnelly, Ludmila Prokunina-Olsson","doi":"10.1089/jir.2023.0122","DOIUrl":"10.1089/jir.2023.0122","url":null,"abstract":"<p><p>It has now been 20 years since the original discovery of the interferon λ (IFN-λ) family (Kotenko et al., 2003; Sheppard et al., 2003) and 10 years since the subsequent discovery of IFN-λ4 (Prokunina-Olsson et al., 2013). The IFN-λ family (type III IFNs) includes 4 members: IFN-λ1, 2, 3, and 4, and all 4 of these proteins signal through the same heterodimeric receptor complex: IFN-λR1 plus IL-10R2. Throughout the past 20 years, much has been learned about the IFN-λ family and the important role of these cytokines in antiviral responses against viruses such as hepatitis C virus, influenza A virus, and SARS-CoV-2. This special issue of the <i>Journal of Interferon & Cytokine Research</i> (JICR) features a group of new reports that highlight recent developments regarding various aspects of IFN-λ-mediated responses. Many of these reports were first presented during the Interferon Lambda 2022 Satellite Meeting after the \"Cytokines 2022\" meeting in Hawaii. These articles underscore the fact that our understanding of the IFN-λ family continues to evolve and remains a critical subject area for additional future research.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"359-362"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interview with Prof. Jorge Kalil: The Challenge of Doing Competitive Translational Research in Brazil.","authors":"","doi":"10.1089/jir.2023.29053.daw","DOIUrl":"https://doi.org/10.1089/jir.2023.29053.daw","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 8","pages":"315-318"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Therapeutic Values of IL-7/IL-7R and the Recombinant Derivatives in Glioma: A Narrative Review.","authors":"Marjan Hesari,&nbsp;Zeinab Attar,&nbsp;Shakiba Soltani-Shirazi,&nbsp;Omid Keshavarzian,&nbsp;Reza Taheri,&nbsp;Reza Tabrizi,&nbsp;Hamed Fouladseresht","doi":"10.1089/jir.2023.0050","DOIUrl":"https://doi.org/10.1089/jir.2023.0050","url":null,"abstract":"<p><p>Interleukin-7 (IL-7) is essential for maintaining the immune system's defense functions by regulating the development and homeostasis of lymphocytes. Findings have shown the high efficacy of IL-7/IL-7 receptor (IL-7R)-based immunotherapy on various malignancies, with confirmation in both animal models and humans. In recent years, the progression-free survival and overall survival of patients suffering from gliomas significantly increased by introducing C7R-expressing chimeric antigen receptor (CAR)-T cells and long-acting IL-7 agonists such as NT-I7 (rhIL-7-hyFc, Efineptakin alfa). However, the effect of IL-7-based immunotherapies on the resistance of tumor cells to chemotherapy (when used simultaneously with chemotherapy agents) is still ambiguous and requires further studies. This article first reviews the pathophysiological roles of IL-7/IL-7R in tumors, focusing on gliomas. Subsequently, it discusses the therapeutic values of IL-7/IL-7R and the recombinant derivatives in gliomas.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 8","pages":"319-334"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Cytokine Profiles in Patients with Rheumatoid Arthritis Before and After Treatment with Methotrexate.","authors":"Manoj Lama,&nbsp;Rajat Sarkar,&nbsp;Bappaditya Ghosh","doi":"10.1089/jir.2023.0078","DOIUrl":"https://doi.org/10.1089/jir.2023.0078","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an inflammatory autoimmune illness affecting around 1% of the population globally. Cytokines have a crucial role in the pathogenesis of RA. The objectives of the present study were to compare the serum cytokine profiles between methotrexate (MTX)-treated and MTX-naive RA patient groups, MTX-treated RA patient group and healthy controls, and MTX-naive RA patient group and healthy controls. Enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-17, IL-6, interferon-gamma (IFN-γ), and IL-10 in 80 RA patients (48 MTX treated and 32 MTX naive) and 80 healthy controls. For all cytokine assays, absorbance was measured at 450 nm using a microplate reader (Bio-Rad). Independent sample <i>t</i>-test was used to compare the serum cytokine concentrations between the study groups using SPSS version 25. MTX-treated RA patient group had significantly reduced serum levels of TNF-α (36.13 ± 17.64 versus 45.82 ± 23.07, *<i>P</i> = 0.037), IL-17 (307.85 ± 151.74 versus 435.42 ± 241.19, **<i>P</i> = 0.006), and IFN-γ (414.93 ± 212.13 versus 527.15 ± 269.61, *<i>P</i> = 0.041) compared to MTX-naive RA patients. Both MTX-treated and MTX-naive RA patient groups had significantly high serum levels of TNF-α, IL-1β, IL-17, IL-6, IFN-γ, and IL-10 when compared to healthy controls (***<i>P</i> < 0.001). Downregulation of the serum concentrations of certain key cytokines, viz. TNF-α, IL-17, and IFN-γ, demonstrates the anti-inflammatory effect of MTX in RA patients.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 8","pages":"344-350"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Characteristics of Early Cytokine Storm Response to Cardiac Surgery.","authors":"Danyang Zhao,&nbsp;Rongli Yang,&nbsp;Sibo Liu,&nbsp;Dong Ge,&nbsp;Xiaolei Su","doi":"10.1089/jir.2023.0044","DOIUrl":"https://doi.org/10.1089/jir.2023.0044","url":null,"abstract":"<p><p>Cardiac surgery can provoke an acute cytokine storm that may contribute to the development of postoperative multiple organ dysfunction syndrome. We prospectively observed patients undergoing cardiac surgery and divided them into two groups: the severe group and the mild group. Healthy individuals were enrolled acting as the control group for comparison. Plasma samples and clinical data were recorded at the initiation of cardiac-pulmonary bypass (CPB) and 3, 6, 12, 24, and 48 h after initiation of CPB. Cytokine levels were detected using the Luminex^® technique. Thirty-nine adults were enrolled in this study (14 in the severe group, 15 in the mild group, and 10 in the control group). Cytokine concentrations were significantly higher in the severe group. Principal component analysis was used to establish a cytokine storm intensity curve, which represented the overall trend of 10 cytokines. The peak concentrations of interleukin (IL)-6, IL-10, and IL-16 were 425.1, 198.5, and 623.0 pg/mL, which were more than 1,200, 1,800, and 240 times the normal level, respectively. The maximum cytokine storm intensity predated the maximum Vasoactive-Inotropic Score (VIS) and Sequential Organ Failure Assessment (SOFA) score in the severe group. Cytokine storm response to cardiac surgery occurred early and was associated with disease severity. Interventions to cytokine storm should be initiated early as guided by cytokine storm biomarkers such as IL-6, IL-10, and IL-16 in severe patients undergoing cardiac surgery. <b><i>Clinical Trial Registration:</i></b> ChiCTR1900021351.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 8","pages":"351-358"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}